Due to the high failure rates, drug development is a very expensive and inefficient process. Few of the millions of compounds generated by chemists are suitable for human use because of their toxicity. There is a major need to reduce the number of animals used in research while increasing the efficiency and reducing the costs of identifying safe and effective drugs. This proposal will support the development and validation of murine stem cell biology used in combination with gene and protein array technologies as a more predictive and cost effective in vitro test for toxic drugs and compounds. Known teratogens or toxins for adult organs (liver, heart, & nervous system) will be evaluated for their effects on the in vitro growth and development of the stem cell-derived tissues. Developing and validating the combination of in-depth protein and gene profiling with the broad clinically relevant biology represented during the in vitro differentiation of stem cells should enable the development of a powerful test system for identifying and recognizing important surrogate markers of human toxicity. The result will be a commercial screening system that will increase the efficiency and reduce the costs of drug development. PROPOSED COMMERCIAL APPLICATIONS: There is a very pressing need in the pharmaceutical industry for technology that increases the efficiency of prioritizing drug leads. Because the costs of development are so expensive and time consuming, working on a drug that will ultimately fail is enormously expensive. The proposed screening system should allow predictive toxicology assessment early during drug development and will be provided to the pharmaceutical industry as a screening service.